This project concerns identification of tissue cells responsible for synthesis of complement components in the guinea pig and man with characterization of the functional significance and metabolic properties of the involved cells in normal and diseased states. In general, appropriate selective modifications of the Jerne hemolytic plaque assay system will be used to identify and count cells synthesizing C4, C3, C5, or C6. Preliminary and other studies have already implicated cells of the reticuloendothelial system in synthesis of several complement components. Attempts to determine the normal and pathologic mechanisms involved in metabolic control of complement component synthesis will be made by assay of dissociated tissue cells from guinea pigs (or in selected instances from humans) treated with a variety of agents known to affect the reticuloendothelial system or activation and utilization of components. Some reagents to be administered to guinea pigs or to be incubated with dissociated guinea pig or human tissue cells as means to assess mechanisms of stimulation or suppression of complement synthesis are yeast zymosan, endotoxin, purified cobra venom factor, anti-macrophage serum, antiserum mono-specifically reative with individual complement components, carageenan, corticosteroid,tuberculin in cases of both normal and BCG sensitized animals, hormones, vitamins, and metabolic inhibitors such as puromycin. In addition to analysis of dissociated cells from selected organs, found to be sites of high numbers of complement synthesizing cells, study will also be made of cells dissociated from embryonic tissue to assess ontogenic cellular development of complement synthesis. Moreover cells dissociated from selected inflammatory infiltrates will be studied to assess possible contributory role of local complement component synthesis and of complement synthesizing cells in selected general and hypersensitivity induced inflammatory reactions. Results of these studies have bearing on the pathogenesis and possible ultimate therapeutic modification of autoimmune and other hypersensitivity inflamatory reactions, transplant rejection reactions, and malignant tumors.